Thalidomide is a racemic compound sold under the trade name THALOMID® and chemically named α-(N-phthalimido)glutarimide or 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione. Thalidomide was originally developed to treat morning sickness, but it was withdrawn from use due to teratogenic effects. Thalidomide is currently approved in the United States for the treatment of erythema nodosum leprosum in humans. Physician's Desk Reference®, pp. 1081-1085 (55th Ed., 2001).
Thalidomide has reportedly been used on patients with leprosy, chronic graft-vs-host disease, rheumatoid arthritis, sarcoidosis, several inflammatory skin diseases, and inflammatory bowel disease. See generally, Koch, H. P., Prog. Med. Chem., 22: 165-242 (1985). See also, Moller, D. R., et al., J. Immunol., 159: 5157-5161 (1997); Vasiliauskas, E. A., et al., Gastroenterology, 117: 1278-1287 (1999); and Ehrenpreis, E. D., et al., Gastroenterology, 117: 1271-1277 (1999). It has further been alleged that thalidomide can be combined with other drugs to treat iscehemia/reperfusion associated with coronary and cerebral occlusion. U.S. Pat. No. 5,643,915.
More recently, thalidomide has been used in the treatment of specific types of cancers. These include refractory multiple myeloma, brain, melanoma, breast, colon, mesothelioma, and renal cell carcinoma. See, e.g., Singhal, S., et al., New England J. Med., 341(21): 1565-1571 (1999); and Marx, G. M., et al., Proc. Am. Soc. Clin. Oncology, 18: 454a (1999). It has further been reported that thalidomide has been used to prevent the development of chronic cardiomyopathy in rats caused by doxorubicin. Costa, P. T., et al., Blood, 92(10:suppl. 1): 235b (1998). Other reports concerning the use of thalidomide in the treatment of specific cancers include combination with carboplatin in the treatment of glioblastoma multiforme. McCann, J., Drug Topics. pp. 41-42 (Jun. 21, 1999). Thalidomide has reportedly also been used as an antiemetic during the treatment of astrocytoma. Zwart, D., Arzneim.-Forsch., 16(12): 1688-1689 (1966). A method of inhibiting of angiogenesis is disclosed by U.S. Pat. No. 6,235,756 B1, which is incorporated herein by reference.
Thalidomide is administered to patients orally. Prior to the present invention, thalidomide was orally administered in a size #0 capsule shell containing 12.5 percent weight by total weight of the composition. The capsule fill weight is 400 mg, so only 50 mg of thalidomide are included per capsule. For use in the treatment of diseases such as cancer, however, 200 mg to 800 mg dosages are commonly required. Therefore, patients had to ingest 4 to 16 capsules of thalidomide to receive a therapeutically effective amount of the drug when treating cancer. Because of the large size of the #0 capsule and the large amount of thalidomide required to treat certain diseases and conditions, patient compliance may be problematic. To be specific, some patients may not take thalidomide in its currently available oral dosage form as often or in the large amounts necessary to effectively treat their disease. Therefore, a need exists for new pharmaceutical dosage forms of thalidomide.